Thrombotic markers in metabolic syndrome subjects exposed to diesel exhaust

Traffic-derived particulate matter (PM) is associated with cardiovascular morbidity and mortality, but the mechanism of this association is unclear. Prothrombotic processes have been linked to PM in epidemiological and animal models, but have not been consistently implicated in controlled human models. Diesel exhaust (DE) is a major contributor to PM. We conducted a controlled human exposure of DE in subjects with metabolic syndrome. The study objective was to evaluate DE exposure effects on prothrombotic markers in a population vulnerable to cardiovascular disease. A randomized, crossover, double-blinded design was used: 16 subjects with metabolic syndrome exposed on 3 different days (≥ 2 wk washout) to DE at 0 (filtered air, FA), 100 μ g PM2.5/m3 (DE100) and 200 μg PM2.5/m3 (DE200). We assessed DE-associated changes in D-dimer, von Willebrand factor (VWF), and plasmin activator inhibitor-1 (PAI-1) at 3, 7, and 22 h after exposure initiation. A DE200-attributable decrease (1.17-fold; CI 1.04 to 1.34) in VWF was noted at 7 h. Significant changes did not occur in other primary endpoints. As previously noted with healthy subjects, strong diurnal patterns in PAI-1 were observed. Thus, in a novel study, we were unable to demonstrate a prothrombotic effect of moderate-dose diesel exhaust exposure in a population at risk for cardiovascular disease.